Project Summary/Abstract The long-term goal of this program of research is to create and implement multimodal biobehavioral interventions that will prevent or delay memory loss in older adults but will initially focus on women with cardiovascular disease (CVD) due to their disproportionately higher risk. This is important as the prevalence of cognitive dysfunction steeply increases with age after 65 years, affecting women more than men, with greater severity and more rapid decline. A leading risk factor for cognitive dysfunction is CVD, and loss of memory is an early-emerging and particularly distressing type of cognitive dysfunction with serious public health consequences. Evidence shows that both physical activity interventions and cognitive training improve memory in healthy older adults and may synergize when combined in a multimodal intervention as each targets different mechanisms. To date, no study testing physical activity interventions and/or cognitive training has targeted older women with CVD despite their disproportionate risk for memory loss. Moreover, existing physical activity interventions that target memory are largely supervised and structured, which can fail to generate long-term behavior change. In contrast, lifestyle approaches emphasizing small behavioral changes to daily life are more likely to be maintained. Older women and adults with CVD prefer lifestyle interventions in the home and community over structured exercise interventions in a gym or lab. Finally, few combined interventions have included serum biomarkers (e.g., brain-derived neurotrophic factor [BDNF], vascular endothelial growth factor [VEGF], insulin-like growth factor 1 [IGF-1]) that may be early indicators of intervention effects. We will build upon the promising findings of our two lines of research: (1) a lifestyle physical activity intervention targeting older women with CVD, and (2) easily disseminated cognitive training with the BrainHQ program in patients with heart failure. The next step of this research program is to analyze the independent and combined effects of a lifestyle physical activity intervention (Move) and cognitive training (Mind) on memory in women ? 65 years with CVD. In the proposed study, we will evaluate the efficacy of the 24-week combined MindMoves on memory performance and memory-related serum biomarkers at 24, 48, and 72 weeks in older women with CVD. Using a 2x2 factorial design, 254 older women with CVD will be recruited from two women?s cardiology clinics and randomized to one of four conditions: (1) Move, (2) Mind, (3) MindMoves, (4) usual care control. Aims are to: (1) determine the independent and combined efficacies of Move and Mind interventions on memory performance, (2) determine the independent and combined efficacies of Move and Mind interventions on memory-related serum biomarkers (BDNF, VEGF, IGF-1), and (3) examine depressive symptoms and genetic factors (APOE-?4 allele, BDNF genotype) as potential moderators of the association between changes in target behaviors and memory. Findings will provide key knowledge about the ability of practical and scalable multimodal lifestyle interventions to target memory in older women with CVD.